Using influenza A and B viruses and the parainfluenza viruses SV5 and Sendai as models, the structure, replication, and interactions with cell membranes of myxoviruses and paramyxoviruses will be studied. The proteins of the virions will be analyzed, with emphasis on the proteins of the viral envelope. Physical and chemical properties will be correlated with specific biological activities of the virus, including receptor binding and neuraminidase activities, virion-induced cell fusion and hemolysis, and RNA transcriptase activity. The precise arrangement of the proteins within the virions, and their roles in virus assembly and in maintaining the structure of the virus will be investigated. This research will be facilitated by methods for the isolation and purification of viral proteins in biologically active form which have been developed in this laboratory, and by the use of virus-cell systems or mutants in which specific defects occur or activation of biological properties can be controlled. These studies are designed to increase our understanding of these biologically important viruses and their mechanisms of pathogenesis, and, in addition, to use these membrane-enclosed viruses as models to provide new information on cell membrane structure and biogenesis. Paramyxoviruses frequently cause persistent infections of cultured cells, and they have been implicated in the causation of several chronic diseases in man and animals. The synthesis of viral macromolecules in cells acutely and persistently infected with the parainfluenza viruses SV5 or Sendai will be studied, and the properties of defective virions will be examined. Such studies should provide information on the mechanims of virus replication and control in persistent infections.